Triiodo-L-thyronine rapidly stimulates alveolar fluid clearance in normal and hyperoxia-injured lungs

Rationale: Edema fluid resorption is critical for gas exchange and requires active epithelial ion transport by Na,K-ATPase and other ion transport proteins. Objectives: In this study, we sought to determine if alveolar fluid clearance (AFC) is stimulated by 3,3′,5 triiodo-L-thyronine (T ₃). Methods: AFC was measured in in situ ventilated lungs and ex vivo isolated lungs by instilling isosmolar 5% bovine serum albumin solution with fluorescein-labeled albumin tracer and measuring the change in fluorescein isothiocyanate-albumin concentration over time. Measurements and Main Results: Systemic treatment with intraperitoneal injections of T₃ for 3 consecutive days increased AFC by 52.7% compared with phosphate-buffered saline-injected control rats. Membranes prepared from alveolar epithelial cells from T₃-treated rats had higher Na,K-ATPase hydrolytic activity. T₃ (10^-6M), but not reverse T₃ (3,3′,5′ triiodo-L-thyronine), applied to the alveolar space increased AFC by 31.8% within 1.5 hours. A 61.5% increase in AFC also occurred by airspace instillation of T₃ in ex vivo isolated lungs, suggesting a direct effect of T₃ on the alveolar epithelium. Exposure of rats to an oxygen concentration of greater than 95% for 60 hours increased wet-to-dry lung weights and decreased AFC, whereas the expression of thyroid receptor was not markedly changed. Airspace T₃ rapidly restored the AFC in rat lungs with hyperoxia-induced lung injury. Conclusions: Airspace T₃ rapidly stimulates AFC by direct effects on the alveolar epithelium in rat lungs with and without lung injury.